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Transient, inhaled gene therapy with gamma interferon mitigates pathology induced by host response in a mouse model of tuberculosis. | LitMetric

AI Article Synopsis

  • Transient transfection using gamma interferon (IFN-γ) in mice infected with Mycobacterium tuberculosis shows potential for improving disease therapy, as it reduces lung and spleen tissue damage.
  • A study tested the effectiveness of a dry powder inhalation (DPI) treatment alone or alongside oral anti-tuberculosis drugs, finding that while DPI improved organ pathology, it did not significantly decrease the number of bacteria.
  • Interestingly, giving the DPI in four doses was more effective than twelve doses in reducing lung lesions, indicating that the timing and dosing may play a crucial role in the therapy's benefits without causing further lung inflammation.

Article Abstract

Transient transfection of the respiratory mucosa of mice infected with Mycobacterium tuberculosis (Mtb) with gamma interferon (IFN-γ) promises benefits in disease therapy. We investigated preclinical efficacy of a dry powder inhalation (DPI) as a stand-alone versus adjunct to oral anti-tuberculosis (TB) chemotherapy in mice. We observed that this host-directed therapy mitigates the gross organ pathology and histopathology of lung and spleen tissue of infected mice receiving the DPI, either alone or as adjunct therapy. However, no statistically significant reduction in Mtb colony forming units (CFU) occurred if mice were given only DPI; but not drugs. We compared one and three doses a week of the DPI over four weeks; with or without concomitant oral drugs. There was no significant difference in lung CFU after four or 12 doses of the DPI alone, but, surprisingly, four doses were qualitatively better than 12 doses in mitigating lung pathology. Nodular lesions on the lung surface and the area occupied by these was significantly reduced after four doses of the DPI, even without oral drugs. Transient transfection with IFN-γ did not induce pathological inflammation of the lungs and airways. We conclude that IFN-γ, as expected of host-directed therapy, 'heals the host; ' but does not 'kill the bug.'

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Source
http://dx.doi.org/10.1016/j.tube.2022.102198DOI Listing

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